Support is requested for the 2nd Conference on the Therapeutic Potential of Kappa Opioids for the Treatment of Pain and Addiction to be held in Boston on April 21-24, 2013. Recent advances in molecular and behavioral pharmacology suggest that novel opioid analgesics selective for the kappa opioid receptor system may provide effective pain relief without having the addiction risk common to mu-selective opioid agonists. New insights from molecular signaling studies suggest strategies to develop kappa opioid agonists lacking the dysphoric effects of the currently available compounds. In addition, the role of the endogenous dynorphin/kappa opioid systems in mediating the dysphoric effects of stress that increase addiction risk and precipitate relapse of drug taking has also strongly stimulated interest in the therapeutic potential of selective kappa opioid antagonists. The proposed, inclusive conference would repeat a very successful conference held in Seattle July 2011 where all of the scientists working on kappa opioid drug development in academic and industrial laboratories presented their results and participated in the open discussions on key topics shaping this research area. In 2013, the molecular, behavioral, and systems pharmacologists will meet again with medicinal chemists and clinical scientists who are actively engaged in research on kappa opioid drugs. We expect that direct discussions of the advances in the field, the current controversies, and the challenges remaining will be extremely fruitful. The hope is that progress in basic research will result in translational advances ultimately providing new therapeutic options for the non- addictive treatment of pain and effective treatments that can reduce addiction risk by enhancing stress-resilience.